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Warburg effect - Nobelisti Otto Heinrich Warburg

 

Nobel palkinnon voittanut tohtori Otto Warburg keksi, että laskemalla kudosten happipitoisuutta 35 % kahden vuorokauden ajaksi, normaalit solut muuttuivat syöpäsoluiksi.

Syöpäpotilailla veren happisaturaatio on normaalia alhaisempi, yleensä noin 60 % luokkaa (pulssioksimetrialla mitattuna).
The Warburg Effect describes the observation that cancer cells, and many cells grown in-vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire.
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http://en.wikipedia.org/wiki/Warburg_hypothesis


Tavalliset syöpähoidot (sytostaattilääkitys ja säteilyhoito) aiheuttavat kehon happipitoisuuden radikaalin putoamisen. Happivajeesta kärsivät kudokset ovat happamia ja runsashappiset alkalisia eli emäksisiä. ---
Mitokondriot tuottavat suurimman osan solun tarvitsemasta energiasta.
Ne muuttavat ravintoaineisiin sidotun kemiallisen energian ATP:ksi, joka on solun pääasialnen energialähde. Mitokondrion matriksissa tapahtuvat mm. pyruvaatin ja rasvahappojen hapetus (b-oksidaatio) ja näitä reaktioita seuraava sitruunahappokierto.

Energiametabolian lisäksi mitokondrioilla on myös muita tehtäviä esimerkiksi solun jakautumisessa ja apoptoosissa, (ohjelmoitunut solukuolema).
Sytokromi c toimii normaalisti mitokondrion hengitysketjussa, mutta vapautuessaan solulimaan se käynnistää apoptoosin eli ohjelmoidun solukuoleman. Mitokondriot osallistuvat myös muuhun solun sisäiseen signalointiin mm. varastoimalla toisiolähetteinä toimivia Ca2+-ioneja ja vapauttamalla ne tarvittaessa.
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http://www.solunetti.fi/fi/solubiolo...on_tehtavat/2/


Glycolysis

 

Anaerobic glycolysis is the transformation of glucose to pyruvate when limited amounts of oxygen (O2) are available. The anaerobic glycolysis (lactic acid) system is dominant from about 10–30 seconds during a maximal effort.
It replenishes very quickly over this period and produces 2 ATP molecules per glucose molecule, or about 5% of glucose's energy potential (38 ATP molecules). The speed at which ATP is produced is about 100 times that of oxidative phosphorylation.


The pH in the cytoplasm quickly drops when hydrogen ions accumulate in the muscle, eventually inhibiting enzymes involved in glycolysis.

The liver later gets rid of this excess lactate by transforming it back into an important glycolytic intermediate called pyruvate; see Cori cycle.
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http://en.wikipedia.org/wiki/Anaerobic_glycolysis
 
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Pyruvic acid is an organic acid, a ketone, as well as the simplest of the alpha-keto acids.

Pyruvic acid supplies energy to living cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactic acid when oxygen is lacking (fermentation).
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http://en.wikipedia.org/wiki/Pyruvate ---
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Cori cycle


The Cori cycle (also known as Lactic acid cycle), named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized back to lactate.
When oxygen supply is insufficient, typically during intense muscular activity, energy must be released through anaerobic metabolism. Lactic acid fermentation converts pyruvate to lactate by lactate dehydrogenase.
 
Overall, the glycolysis part of the cycle produces 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis part.
 
Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules indicates that the Cori cycle shifts the metabolic burden from the muscles to the liver.
Significance The cycle's importance is based on the prevention of lactic acidosis in the muscle under anaerobic conditions. However, normally before this happens the lactic acid is moved out of the muscles and into the liver.
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http://en.wikipedia.org/wiki/Cori_cycle
 
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Membrane transport protein

A membrane transport protein (or simply transporter) is a membrane protein[1] involved in the movement of ions, small molecules, or macromolecules, such as another protein across a biological membrane.
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http://en.wikipedia.org/wiki/Membrane_transport_protein

Calcium pump

There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important for cells to maintain low concentrations of Ca2+ for proper cell signalling; thus it is necessary for the cell to employ ion pumps to remove the Ca2+.
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http://en.wikipedia.org/wiki/Calcium_pump

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Warburg effect

The phrase "Warburg effect" is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.

Basis In oncology, the Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria as in most normal cells.
 
The latter process is aerobic (uses oxygen). Malignant, rapidly growing tumor cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful.
Possible explanations of the effect The Warburg effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumors, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's apoptosis program which would otherwise kill cancerous cells. It may also be an effect associated with cell proliferation. Since glycolysis provides most of the building blocks required for cell proliferation, cancer cells have been proposed to need to activate glycolysis, despite the presence of oxygen, to proliferate.
Glycolytic inhibitors Clinical trials are ongoing for 2-DG and DCA
 
 


Katso myös: Minkä värisiä syöpäkasvaimet ovat?  Alla maksasyöpä, valkoinen kasvusto. Linkki
 
 

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